Anaerobic Manufacturing and Molecular Analytical Process Optimization to Support Clinical Development of Live Biotherapeutic Products

厌氧制造和分子分析过程优化支持活生物治疗产品的临床开发

基本信息

批准号：
10482472
负责人：
Ricardo Valladares
金额：
$ 97.91万
依托单位：
SIOLTA THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-04 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10482472
关键词：
Acute Allergens Allergic Allergic Disease Allergic inflammation Anaerobic Bacteria Anaphylaxis Antioxidants Asthma Atopic Dermatitis Bacteria Biochemical Pathway Biological Markers Biological Response Modifier Therapy Bioreactors Cells Child Childhood Chronic Clinical Clinical Research Clinical Trials Cyclic GMP Data Set Desiccation Development Disease Disease model Economic Burden Environmental Risk Factor Eosinophilia Evaluation Excipients Extrinsic asthma Feces Flow Cytometry Food Hypersensitivity Formulation Freeze Drying Freezing Goals Healthcare Human Hypersensitivity IgE Immediate hypersensitivity Immune Immune Tolerance Immunologics Impairment Individual Infant Infiltration Interleukin-4 Intervention Lactobacillus Licensing Life Link Lung Lymph Mediating Metagenomics Methods Microbe Molecular Morbidity - disease rate Onset of illness Oral Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phase II Clinical Trials Powder dose form Prevention Primary Prevention Probiotics Process Production Public Health Quality of life Reaction Recovery Regulatory T-Lymphocyte Reporting Risk Secondary Prevention Supplementation Symptoms System Temperature Testing Th2 Cells Therapeutic Training United States Food and Drug Administration Update Validation Work allergic airway inflammation analytical method base capsule clinical development clinical efficacy clinical material commensal bacteria commercialization cost design disorder prevention disorder risk global health gut microbiota immunoregulation improved in vivo innovation liquid formulation member method development microbial mouse model novel novel strategies potency testing pre-clinical prevent process optimization product development programs standard of care success therapeutic candidate

项目摘要

ABSTRACT Allergic diseases including atopic dermatitis, food allergy, and allergic asthma represent a global health problem that disproportionately impacts children. Surprisingly, there are no approved approaches to prevent the development of these diseases in at-risk individuals, resulting in chronic morbidity and economic burden. The management of asthma, for example, carries a steep cost burden of billions of dollars per year in the US alone, of which nearly 20 billion is spent on standard of care treatments with variable efficacy. Food allergy management is generally limited to allergen avoidance and rescue from severe acute anaphylaxis. There is a crucial need to develop innovative strategies to prevent the onset of these Type 1 allergic diseases rather than treating their symptoms. A preventative approach targeting at-risk individuals could significantly reduce the morbidity and healthcare burden associated with these increasingly common conditions. Studies confirm the link between gut microbiota development, immunological training, and allergic disease onset in childhood, and it is now clear that allergic disease risk is associated with aberrant microbial exposures over the first year of life. Longitudinal gut microbiota profiling studies in infants and children show that a loss of specific immunomodulatory commensal bacteria, and their metabolic networks, precedes allergic disease development. Using infant gut microbiota data sets and in vivo allergic disease models, Siolta Therapeutics has designed a live biotherapeutic product (LBP), STMC-103H, to stimulate tolerant immunological development and prevent allergic disease onset in at-risk individuals. STMC-103H contains three distinct active ingredient bacteria isolated from healthy human stool. Siolta has performed extensive cGMP manufacturing development, including formulation, process, and analytical method development, to support Phase 1 and Phase 2 clinical trials of STMC-103H under an IND with the FDA. In this project, we will build on our previous STMC-103H drug product development to improve the stability, potency, and characterization approaches for late-stage clinical trials and subsequent commercialization. Success of this project will directly support the regulatory and commercial development of STMC-103H. Indirectly, this work will improve the manufacturing and clinical development of diverse candidate LBPs containing sensitive live bacteria with high therapeutic potential. Siolta will also seek to license novel manufacturing approaches to other LBP developers.

抽象的过敏性疾病，包括特应性皮炎，食物过敏和过敏性哮喘代表了全球健康问题这不成比例地影响儿童。令人惊讶的是，没有批准的方法来防止这些疾病在高危人群中的发展，导致长期发病和经济负担。这例如，哮喘管理的管理每年在美国就会承担每年数十亿美元的巨额负担其中将近200亿次用于具有可变功效的护理水平。食物过敏管理通常仅限于避免过敏原的避免过敏原，并从严重的急性过敏反应中挽救。至关重要制定创新的策略，以防止这些类型1的过敏性疾病的发作，而不是对待其症状。针对高危个人的预防方法可以显着降低发病率和与这些日益常见的条件相关的医疗保健负担。研究证实了肠道菌群发展，免疫学训练和过敏性疾病发作之间的联系在童年时期，现在很明显，过敏性疾病风险与异常微生物暴露有关生命的第一年。婴儿和儿童的纵向肠道菌群分析研究表明，特定的丧失免疫调节的共生细菌及其代谢网络先于过敏性疾病发展。使用婴儿肠道菌群数据集和体内过敏性疾病模型，Siolta Therapeutics设计了一种实时生物治疗产品（LBP），STMC-103H，以刺激耐受性免疫发育并防止高危个体中的过敏性发作。 STMC-103H包含分离的三种不同的活性成分细菌来自健康的人粪便。 Siolta进行了广泛的CGMP制造开发，包括制定，过程和分析方法开发，以支持第1阶段和第2阶段的临床试验 STMC-103H在IND下与FDA。在这个项目中，我们将基于以前的STMC-103H药物开发，以提高稳定性，后期临床试验和随后的商业化的效力和表征方法。该项目的成功将直接支持STMC-103H的监管和商业发展。间接地，这项工作将改善各种候选LBP的制造和临床开发含有具有高治疗潜力的敏感活细菌。 Siolta也将寻求许可对其他LBP开发人员的制造方法。